Development of Mitochondria-Targeted Small-Molecule Dyes for Myocardial PET and Fluorescence Bimodal Imaging

Abstract

Mitochondria-targeting positron emission tomography (PET) and fluorescent dual-modal probes are rarely reported. As one of the most promising lipophilic cations, F16 and its derivatives (F16s) have never been used for myocardial imaging. In this work, 14 F16s are synthesized and evaluated for cardiac imaging. In vitro cell fluorescence imaging revealed that the lead probe 5MEF is precisely localized in the mitochondria of cardiomyocytes. In addition, it shows excellent ex vivo fluorescence imaging quality with the heart-to-muscle and heart-to-liver ratios up to ∼2. Furthermore, the radiofluorinated probe 18 F-5MEF is successfully prepared and shows a high initial heart uptake of 8.66 ± 0.34 % ID/g at 5 min post injection. It displays a high heart imaging performance, a long retention time in the heart, and a low background in the most normal tissues as revealed by PET. To our knowledge, this is the first time novel F16 analogues are designed and developed for myocardial dual-modal imaging.

Biomarkers of aging

“…Advancing age induced oxidative stress and inflammatory factors accumulation has been linked with cardiovascular aging, which usually develops cardiovascular diseases in the elderly (López-Otín et al, 2023). F-5MEF (a dual-modal probe) was synthesized and achieved mitochondria-targeting myocardial dual-modal imaging (Zheng et al, 2022). Besides, 18 F-sodium fluoride ( 18 F-NaF) showed promising use in characterizing culprit atherosclerotic plaques in the carotid circulation (Kaczynski et al, 2022).…”

Highlight selection of radiochemistry and radiopharmacy developments by editorial board

“…A novel class of 18 F-labeled mitochondrial-targeted (E)-4-(1H-Indol-3-ylvinyl)-N-methylpyridinium iodide (F16) compounds was synthesized and evaluated for myocardial positron emission tomography (PET) and fluorescence bimodal imaging (Zheng et al 2022). F16 is a lipophilic cation which is often used in mitochondria-targeted tumor imaging and treatment.…”

Harnessing the power of molecular imaging for drug discovery and development

“…Molecular imaging is a new generation of imaging modality that employs contrast agents to enable in vivo qualitative and quantitative analysis and detection of physiological processes at the molecular level, thus providing information unavailable through traditional imaging modalities [1], such as optical imaging [2][3][4], ultrasound imaging [5,6], magnetic resonance imaging (MRI) [7][8][9], single-photon emission computed tomography (SPECT) [10], and positron emission tomography (PET) [11][12][13]. Molecular optical imaging based on phenomena such as fluorescence, Raman scattering, chemiluminescence, and bioluminescence is widely used for disease diagnosis, drug development, and pathological analysis owing to its high sensitivity, high contrast ratio, high resolution, and high imaging speed [14,15].…”